利用微流道尺寸過濾血漿之微流體晶片

Microfluidic Chip for Blood Plasma Separation Based on Channel Size Filtration

林伯育(Bo-Yu Lin)

指導教授 ： 郭如男

國立虎尾科技大學/工程學院/自動化工程研究所/碩士(2015年)

https://doi.org/10.6827/NFU.2015.00014

摘要

血漿裡面含有各種疾病的因子以及病毒細菌等等的抗原與抗體等，所以血液疾病檢測的第一步驟常常需將血球與血漿分離。本研究的目的是在利用微機電技術設計製作血漿分離晶片來進行血漿與血球細胞的分離，分離出的血漿可以進一步作為待測物來進行生醫檢測。本研究是利用微流道內部結構的尺寸大小來進行血漿分離的動作，基板是以載玻片為材料(厚度為 1~1.2 mm)，再經由黃光微影製程及濕式蝕刻方式蝕刻出微流道，將流道深度控制在 2 μm 內，以阻擋血液中的細胞過濾出血漿流入收集血漿的流道。上蓋部份是以矽晶圓為基板，進行黃光微影製程來製作出 SU-8 的母模，再將PDMS 澆注在母模進行翻模完成上蓋 PDMS 部分。基板及上蓋經氧電漿改質後進行接合即完成血漿分離晶片，改質將材料變為親水性表面，利用毛細管力作為推動全血的驅動力進行血漿分離的動作。實驗結果顯示此血漿分離晶片可達到 0.01μl/s 的血漿流率，對往後進行血漿中疾病檢測時可減少血球細胞的干擾而造成檢測誤差。本研究血漿分離晶片應用於肌酐酸檢測樣本的濃度在 0.11∼1.78 mg/dL（10∼160 μM），結果顯示檢測靈敏度可達12.68 count/μM，線性度為 95.38%。另應用於凝血酶原時間檢測，過濾出的血漿與凝血酶原試劑混合後隨著時間增加而產生凝固反應，實驗結果顯示 20 組凝血酶原時間檢測其平均時間為 13.3秒。

關鍵字

血漿 ； 微流道 ； 濕式蝕刻 ； 毛細管力 ； 肌酐酸 ； 凝血酶原時間

並列摘要

Blood plasma contains various kinds of antigens and antibodies due to disease factors, viruses, bacteria, etc.; therefore, the first step for blood disease detection is to separate blood cells and blood plasma. This research intends to adopt MEMS technology for its design of a blood plasma separation chip that can separate blood plasma and blood cells, and the separated blood plasma can be used as a determinand for further biomedical detection. In the proposed device, the whole blood is introduced into the microfluidic chip by means of capillary forces and the plasma is then extracted from the whole blood via a size exclusion effect in the filtration channel. The depth of the filtration microchannel less than 2 μm which can be extract plasma from the whole blood. The microfluidic chip is fabricated from a single polydimethylsiloxane (PDMS) mold and sealed with an etched glass substrate. The experimental results show that the blood plasma separation chip can bring blood plasma’s flow rate up to 0.01 μl/s, which effectively reduces the error that may be triggered by blood cells during subsequent disease detection testing on blood plasma. The feasibility of the proposed device for clinical applications has been demonstrated by performing creatinine and prothrombin time (PT) tests. The sample concentration is 0.11~1.78 mg/dL (10~160 μM), with a detection sensitivity of 12.68 count/μM, and degree of linearity of 95.38%. For the 20 blood samples considered in the PT tests, the mean time required for coagulation was determined to be approximately 13.3 s.

並列關鍵字

Capillary ； Creatinine ； Microchannel ； Plasma ； Prothrombin time ； Wet etching

參考文獻

[26] 邱繼鋒，2007，“血液在表面張力驅動微流道內之分析”，國立台灣大學工學院應用力學研究所，碩士論文。

[28] 邱繼鋒，2007，“血液在表面張力驅動微流道內之分析”，國立台灣大學工學院應用力學研究所，碩士論文。

[41] 陳冠宇，2007，“微流道毛細填充流動之理論與實驗研究”，淡江大學機械與機電工程系，碩士論文。

[1] N. Vandelli, D. Wroblewski, M. Velonis, and T. Bifano, 1998, “Development of a MEMS microvalve array for fluid flow control,” J. of Microelectromechanical Systems, vol. 7, no. 4, pp. 395-403.

[2] K. S. Yun, I. J. Cho, J. U. Bu, C. J. Kim, E. Yoon, 2002, “A surface-tension driven micropump for low-voltage and low-power operations,”J. Microelectromech. Systems., vol. 11, no. 5, pp. 454-461.